6/18/2019

Emerging Technologies in Diabetes Care

Lindsey M. VanDyke, D.O. Methodist Mansfield Endocrinology Associates Mansfield, TX

Conflicts to Disclose

Stock holdings:

Emisphere Technologies Novo Nordisk Abbott Laboratories

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“2019 is The Year to have a diagnosis of diabetes…”

“...because we’ve never had technology like we have now.” - Me

Objectives ● The options to treat diabetes are as varied as the patients we share ● Review current available options for diabetes care ○ Novel insulins ○ CGMs ○ Insulin pumps ○ Patch pumps ○ Smart pens ● Consider how embracing technology can improve outcomes by reducing burden of care ● Review outcome data for various approaches to management ● Outline what is on the horizon in the next 1-2 years ● Provide resources for quick reference

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Why Do We Care?

Diabetes Technology: What You Will See

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Glucose Monitors

● In 2016, FDA required that all home glucometers had to be within 20% of the true glucose 99% of the time.

● If venous glucose = 100 ○ CBG can be 80-120 and be acceptable

Courtesy: UCSF mini med school

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Continuous Glucose Monitors (CGMs) ● Other than a venous glucose, they are the most precise way to measure a patient’s glucometrics. ● Real-time observation allows patients to engage more in their lifestyle interventions ○ Can produce 0.5-1% reduction in a1c alone ● Important for safety in the setting of “brittle” patients or those who no longer retain hypoglycemia awareness. ● Allows those with visual/auditory disabilities various ways to understand what their glucose is doing. ● Helps ensure monitoring of sugar fits into the patient’s life. ● Allows for the usage of Time In Range metric

Continuous Glucose Monitors (CGMs)

● Not all CGMs are created equal! ● Guidelines differentiate between Real Time and Intermittent Flash glucose sensing. ○ RT-CGM is endorsed for Type 1 Diabetes ○ IF-CGM OR RT-CGM can be appropriate for Type 2 Diabetes

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CGMs: Abbott Freestyle Libre

● Manufacturer: Abbott ● Release dates: ○ 10d sensor in 2017 (12h warmup) ○ 14d sensor in 2018 (1h warmup) ● MARD averages 9.4% (8.5 - 10.8%) ● First factory calibrated sensor ● FDA approved for insulin dosing ● Medicare DME coverage if taking 4 shots/day and checks glucose 4x/d. ● Private coverage typically $75/month cap. ● Cost effective if pt checking > 3x/d

CGMs: Abbott Freestyle Libre

● Cash: typically each 14d sensor ~$60 and reader is $70-100 once. ● As of June 2019 ○ Freestyle LibreLink app replaces reader for BOTH Android as well as iPhone 7 & higher. ● Imperfect alternative to consider: ○ Use of 1 sensor every 90 days instead of CBGs ○ Cash cost averages to $240/year or $20/month.

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CGMs: Dexcom G6 ● Manufacturer: Dexcom (CA) ● Release date: 2018 ● Vastly simplified applicator ● 10 day wear ● 2 hour warm up time ● Factory calibrated & FDA approved for insulin dosing ● Measures interstitial glucose every 5 minutes ● Alerts can be shared with up to 5 people and connects to phone apps and smart devices. ● Sensor filament is the thickness of 2 human hairs ● Pharmacy benefit or DME

CGMs: Eversense

● Manufacturer: Senseonics (MD) ● US Release date: 2018 ● The world’s first implantable CGM ● MARD 8.5% ● Daily calibrations: 2 ● FDA approved for insulin dosing ● First to use fluorescent glucose-polymer indicating technology. ● Currently approved for 90 day wear ● Transmitter is applied with new adhesive daily ● Implant safe for most MRIs ○ Transmitter must be removed

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CGMs: Eversense

● Senseonics XL was approved in Europe for 180 day wear in 2017. ● Studies underway for 180 day approval in US. ● Cons: ○ Requires 2 calibrations/day ○ 24h warmup ● Next from Senseonics ○ Eventual Eversense 365 - 1 year wear ○ Factory calibration ○ Integration to other devices

CGMs: Guardian

● Manufacturer: Medtronic (CA) ● Release date: 2018 ● Daily calibrations: 2-4 ● MARD 8.7% ● 7 day wear ● 2 hour warm up time ● NOT FDA approved for insulin dosing

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Who Has the Best Sensor?

● n=23, in vivo crossover trial over 6 weeks ● Each patient wore all 3 sensors and utilized Nova Biomedical Stat Strip Xpress meter for calibrations ● Nominal MARDS (2277 data sets) ○ Eversense 14.8% ○ Dexcom G5 16.3% ○ Libre Pro 18% ● The difference in MARD between Eversense and Dexcom G5 p = 0.008 ● Point accuracy of Eversense was superior

Other Cutting Edge Resources

● Tidepool Loop - originated as an open source DIY project for “hacking” insulin pumps and producing algorithms for automated closed loop delivery. ○ Pending FDA approval for the Loop app now ○ Partnership with Omnipod underway ○ Plans to remain open source to partner with other devices ● Coaching ● Livongo

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Novel Approaches to Medications

● SGLT2/SGLT1 combinations are now before the FDA for use in Type 1 Diabetes. ○ Timeline is undetermined ● Semaglutide (Ozempic) will be the first GLP1a available as daily oral medication ○ Anticipated in Q4 2019

Oral GLP-1a: How’d They Do It?

● Engineer: Emisphere Technologies ● Famous for oral B12 ● Molecule: SNAC ○ Carrier molecule facilitates peptides through the GI layers. ○ Does not interact with therapeutic rider. ○ Improves bioavailability of drug. ● Technology could facilitate oral options for many agents ○ Insulin ○ Heparin/LMWH ○ calcitonin/PTH

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Oral GLP-1a: What Can We Expect?

● PIONEER trials demonstrated equivalent lowering a1c. ○ n = 711 randomized placebo controlled crossover trial ○ PO semaglutide vs. liraglutide ○ Primary endpoint: change a1c ● Secondary endpoints: ○ weight loss, adverse events, hypoglycemia, a1c < 7% ● Injectable semaglutide still superior for weight loss.

Insulins

● Still the most powerful way to control a1c ○ Pros: quick reduction in a1c and alleviates glucose toxicity ○ Cons: patients hate the concept of insulin, it’s not “smart”, and it is tricky to navigate. ● Newest agents are novel molecules → improved stability & duration of action ○ Available in concentrated forms for smaller depot and better absorption ● There is a growing movement to make insulin analogues affordable for more patients. ○ Sanofi $99 - $120 offer ● NPH insulin from walmart is $25/vial ○ Equally effective, but with hypoglycemic costs ○ Everyone should have NPH as an emergency back up plan

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Insulins: Afrezza

● Manufacturer: Mannkind (CT) ● Release date: 2015 ● Easy-to-use “whistle” for administering inhaled insulin. ○ Cartridges available in 4u, 8u and 12u ● Rapid onset - take it with the first bite of a meal ● Great for patients who don’t want to use a needle in public ● Flexible dosing & minimal concern for stacking: ○ multiple corrections if consuming a high fat or high protein meal.

Insulins: Afrezza

● NOT appropriate for patients with underlying lung disease. ● Requires peak flow on the chart. ● Frequently requires specialty pharmacy to facilitate approval. ○ Cedra - Dallas & Houston

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Insulins: Afrezza

● Randomized Controlled Clinical CGM Trial, n = 60 DM1 patients ○ Control arm: MDI with aspart ○ Treatment arm ■ Aspart conversion ratio, AC ■ Post-prandial correction protocol ○ Dexcom G5 real time CGM ● Primary endpoint: Time in Range ● Secondary endpoints: change a1c, hypoglycemia, hyperglycemia and variability

Improved Time-in-Range (TIR) on Continuous Glucose Monitor (CGM) with Technosphere Inhaled Insulin (TI) Compared with Insulin Aspart in T1D Patients—STAT Study JANET K. SNELL-BERGEON, HALIS K. AKTURK, AMANDA REWERS, BRUCE W. BODE,LESLIE J. KLAFF, ANNE PETERS, TIMOTHY S. BAILEY, SATISH K. GARG Diabetes Jul 2018, 67 (Supplement 1) 1017-P; DOI: 10.2337/db18-1017-P

Insulin Smart Pen: The New Standard

● Manufacturer: Companion Medical ● Release date: 2019 ● Team from Tandem, Dexcom & Medtronic ● Acts as an “intermediate” insulin pump ● ½ unit dosing ● Patient uses a normal basal pen injection once or twice daily ● The smart pen is loaded with insulin and the app tracks the same data that a pump would: ○ Time and volume of last dose ○ Insulin on board ○ Total daily dose ○ Carb and correction ratios ○ Dose calculator

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Insulin Smart Pen: The New Standard

● Order a Novo-style or a Huma-style pen. ● Patients can choose blue, grey or pink colors. ● Order the Novolog or Humalog in cartridges--these are not interchangeable. ● Copay for 1 pen is $18 on average. ● Each pen lasts 1 year. ● Reminds patients when insulin is expiring. ● Alerts patients to insulin temperature changes. ● Be on the lookout for other Smart Pens to enter the market ○ NovoPen6 & NovoPen Echo in Europe

Insulin Pumps

● Unequivocally the standard of care among type 1 diabetes patients ● Growing number of type 2 diabetes patients are utilizing pump technology ● Hybrid closed loop “artificial pancreas” was released by Medtronic in 2017 and more are on the way ● Expect new names to enter the market ○ Bigfoot ○ Tidepool ○ BetaBionic

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Insulin Pumps: Medtronic 670G

● Release date: 2017 ● Basal rates adjust to accumulating data from Guardian sensor for 6 days. ● NO automated changes to I/C or SF ratios ● NOTE: if a Medicare patient is wearing a Guardian and tries to get approval for another CGM, CMS will NOT accept any data from the Guardian sensor.

Insulin Pumps: T-slim X2

● Manufacturer: Tandem (CA) ● Release date: 2018 ● First updateable insulin pump ● Coordinates with Dexcom G5 & G6 for basal-IQ suspend feature. ● Coming soon: Closed Loop system, Q4 of 2019 will feature Control IQ algorithms ○ All X2 pumps can receive the update ○ New Rx and online training required to unlock the auto features. ○ Algorithm will automate both basal rates and correction boluses. ○ Carb boluses will remain manual.

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Insulin Pumps: What’s Next From Tandem?

● T-slim X2 mobile app: 2019-2020 ○ Allow user to review data without handling pump ○ Allow for remote caregiving ○ Integration to other smart devices is expected. ● T-sport Pump: 2020-2021 ○ Half the size of the current T-slim ○ NO device screen, all controls handled through app ○ Can choose short (patch pump) or long tubing.

Insulin Pumps: Omnipod

● Manufacturer: Insulet (MA) ● Release date: 2010 ● DASH system released 2019 ○ Smartphone style interface ○ Allows for data to be sent to other caregivers ● To-date the only “tubeless” insulin pump ● Coming in 2020: Omnipod Horizon hybrid closed loop system. ○ Partnered with Tidepool Loop for an on- pod algorithm ○ All controls through DASH or phone app ○ Will remain on automatic delivery even if apps are out of range. ○ Expected Q2-Q3 2020

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Insulin Pumps: Next From Omnipod

● ETA: 2020+ ● Expanding the use of the DASH system ● The pod itself will be redesigned for on- body analytics. ● Plans to expand the Type 2 market with a concentrated insulin delivery system. ● Stay tuned...

Insulin Pumps: Vgo “Patch” Pump

● Manufacturer: Valeritas (CA) ● Release date: 2010 ● Fill with rapid acting analogue ● Uses clockspring for 1 basal rate ● Bolus button delivers 2 u per “click” ● Comes in 3 basal rates ○ 20 u basal + up to 36 u prandial ○ 30 u basal + up to 36 u prandial ○ 40 u basal + up to 36 u prandial ● Price: usually the same or less than MDI with insulin analogues

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Insulin Pumps: Vgo “Patch” Pump

● VGO -1.82% & -1.98% ● MDI -0.98% & -1.34% ● Tx Difference -0.84%

P < 0.001 compared to baseline

Lajara,R. et al. Endocrine Practice. 2016; 22(6) 726-735.

Insulin Pumps: Vgo “Patch” Pump

● Achieve reduction of TDD by: ○ Reducing the number of injections per day ○ Optimizing consistency of dosing ○ Minimizing human error ● This phenomenon was consistently clinically beneficial across strata by the 7 month mark. ○ Statistically significant among the 5-15y duration of diabetes strata.

Harrison HC, Everitt B, Nikkel C. Poster: The Impact of utilizing a novel insulin delivery device in patients with type 2 diabetes. AACE 2017.

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Insulin Pumps: Paq Meal & Paq Total “Patch” Pumps

● Manufacturer: CeQur (Switzerland/MA) ● ETA: ?? ● Same concept as the Vgo, with some improvements ● Wearable patch for 3 days ● 7 different basal rates ● Maximum daily dose: 110 units

Mader JK, Lilly L, Aberer F, Poettler T, Johns D, Trautmann M, Warner J, Pieber T. 2018. Improved glycaemic control and treatment satisfaction with a simple wearable 3‐day insulin delivery device among people with Type 2 diabetes. Diabetic Medicine. 35(10):1448–1456.

Insulin Pumps: Paq Meal & Paq Total “Patch” Pumps

● Crossover clinical trial, n = 24 ● Baseline assessments ● Transition phase of at least 6 days ● 12 weeks treatment ● Significant changes in a1c realized at weeks 8.6% + 3.2% 8 (p = 0.0001) & week 12 (p < 0.0001)

7.2% + 2%

● NOTE: study funded, overseen and analyzed by CeQur

Mader JK, Lilly L, Aberer F, Poettler T, Johns D, Trautmann M, Warner J, Pieber T. 2018. Improved glycaemic control and treatment satisfaction with a simple wearable 3‐day insulin delivery device among people with Type 2 diabetes. Diabetic Medicine. 35(10):1448–1456.

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Insulin Pumps & More: Bigfoot Biomedical

● ETA: ?? (overdue) ● They ask the same question: “how to reduce the burden of diabetes care?” ● Developing subscription based support and bundled supplies ● Connected pens ● Closed loop system with [disposable] pump and CGM ● All overseen by developing artificial intelligence

Courtesy: Park Nicollet International Diabetes Center

Insulin Pumps & More: Beta Bionics

● Originated at Boston University ● ETA: ?? ● Integrated insulin-dasiglucagon analogue pump ● Randomized in vivo crossover trial underway ● A 3-in-1 device with life long, machine-learning for individualized glucose control ● Claim fully autonomous control--no carb counting, adjusting rates or manual boluses

courtesy : Beta Bionics

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www.aace.com

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Additional Resources

For you:

Lindsey M. VanDyke

O: 817 - 453 - 7707

[email protected]

Diabetes Technology Night - November 2019

For the Patients:

Podcast: The Endo Days

YouTube Channel: Mansfield Endocrine

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